British Columbia Medical Journal, October 2010 issue: Clinical features and pathogenetic mechanisms of osteo - arthritis of the hip and knee

www.bcmj.org VOL. 52 NO. 8, OCTOBER 2010 BC MEDICAL JOURNAL 393

ABSTRACT: Osteoarthritis is a non-

inflammatory form of arthritis that

accounts for 25% of visits to primary

care physicians. When osteoarthritis

affects the hip and knee, it can lead

to major disability and compromised

quality of life. Diagnosis relies on

clinical symptoms, physical find-

ings, and radiographic findings. The

interplay between mechanical and

systemic factors such as congenital

abnormalities, obesity, and malalign-

ment may predispose individuals to

osteoarthritis of the hip and knee.

We must identify these factors and

the underlying causes of osteoarth -

ritis if we are to develop more pro-

gressive early interventions for this

common affliction.

Osteoarthritis (OA) is a non-inflammatory form of arth -ritis. A common miscon-ception is that OA is due

solely to wear and tear, since OA istypically a disease of persons in thesixth decade and beyond. “Degenera-tive arthritis” is often used as a syno -nym for OA, but OA is not the result ofa bland degenerative process; rather,OA involves both degenerative andregenerative processes.

OA is common and serves as the

main source of chronic joint com-

plaints in adults. The morbidity con-

ferred by OA of the knee and hip in an

ever-aging population is major. Its

high prevalence and huge impact on

quality of life demand that we engage

in better understanding of OA by con-

sidering diagnostic, epidemiological,

clinical, and radiographic features. An

understanding of how OA is classified

and OA risk factors is also critical.

Diagnosis andepidemiologyThe diagnosis of OA relies on clinical

symptoms, physical findings, and

radiographic findings. Not all persons

who have radiographic OA have clin-

ical disease. Conversely, not all per-

sons who have joint pain demonstrate

plain radiographic findings of OA.

Thus, there is often discordance be -

tween X-ray findings and symptoms

of OA.1

OA accounts for 25% of visits to

primary care physicians, and 50% of

NSAID prescriptions.2 It is estimated

that up to 80% of the population will

have radiographic evidence of OA by

age 65, with 60% of those showing

symptoms and thereby having clinical

OA.3 Another study found that by age

70 to 74 years, about 33% of men and

40% of women will have OA with

clinical and X-ray features.4 The life-

time risk of developing symptomatic

knee OA is about 45%, rising to 66%

in obese persons. While there is vari-

ation in these numbers, it is clear that

the morbidity and disability conferred

by OA of the hip and knee is enormous

and demands our attention.5

Symptoms and physical findingsThe main symptoms of OA of the knee

or hip are pain, stiffness, and altered

function. Initially this tends to be

worse with weight bearing and ambu-

lation. Eventually this can progress to

Clinical features and patho-genetic mechanisms of osteo -arthritis of the hip and kneeUnderstanding how osteoarthritis develops is critical to treating thisdisabling disease.

Manal Hasan, MBBS, MD, Rhonda Shuckett, MD, FRCPC, Diplomate ABIM

Dr Hasan is a rheumatology fellow in theDivision of Rheumatology at the Universityof British Columbia, sponsored by the King-dom of Saudia Arabia. Dr Shuckett is a clin-ical associate professor in the Division ofRheumatology at UBC.

BC MEDICAL JOURNAL VOL. 52 NO. 8, OCTOBER 2010 www.bcmj.org394

al compartment OA of the knees. Less

commonly, patients may present with

a valgus or knock-knee deformity,

indicative of more advanced disease

in the lateral compartment of the knee.

On occasion, and much less common-

ly, patients may present with isolated

OA in the patellofemoral joint, which

can of itself be very symptomatic.

In the case of the hip, a true cap-

sular pattern of limitation is found

with groin or buttock pain (or both)

and particular pain with internal rota-

tion of the hip. Flexion deformity of

the involved hip can be present with

advanced OA. Patients will often walk

with a limp, and a waddling Trende-

lenburg gait may be evident in late

stages.

X-ray findings Standard knee X-rays should include

a standing anteroposterior (AP) view

of both knees, plus lateral views. In

patients with suspected posterolateral

OA with a mild valgus de formity, a

30 degree flexed standing pos teroan-

terior (PA) view with the beam

directed 15 degrees from cephalad to

caudad may be valuable in showing

the disease in the posterior aspect of

the lateral compartment of the knee.6,7

In early cases, a standard standing AP

view may appear normal or indicate

very mild OA, whereas the standing

flexed PA view may show bone-

on-bone contact. Patellofemoral OA

of the knee cap is also a common

finding, best diagnosed on a skyline

X-ray view.

X-rays of the hips to evaluate for

OA should include a standing AP

pelvis view and frog-leg views of the

suspected hip joint. It is important to

always order standing X-rays of both

knees in the case of suspected knee

OA and an X-ray of the pelvis and not

just the affected hip in the case of sus-

pected hip OA. This will allow for

comparison between sides and im -

Clinical features and pathogenetic mechanisms of osteo arthritis of the hips and knees

pain day and night once cartilage loss

leads to bone-on-bone contact. True

hip pain is felt in the groin most com-

monly, but can also present in the but-

tock and often down the anteromedial

thigh to the knee. Not uncommonly,

patients may present solely with knee

pain when the problem is in the hip.

Pain arising from osteoarthritis of the

knee is felt right around the knee joint,

and unlike pain caused by hip OA, this

pain does not typically radiate.

In contrast to inflammatory arthri-

tides such as rheumatoid arthritis, with

their prolonged morning stiffness and

worsened pain in the morning, OA

tends to worsen as the day progresses.

The stiffness in OA is termed “inac-

tiv ity stiffness” and contrasts with

the prolonged “morning stiffness” of

rheumatoid arthritis. Inactivity stiff-

ness in osteoarthritic lower limb joints

lasts about 5 to 10 minutes and occurs

when the patient gets up and bears

weight after prolonged immobility.

On physical examination, a small

effusion with a fluid bulge sign can be

present in OA of the knee. Larger effu-

sions can occur but are less frequent

than in the inflammatory arthropathies.

Synovial fluid analysis after aspira-

tion of an OA knee effusion reveals

that the fluid is thick and viscous with

a low synovial white blood cell count,

most of which are mononuclear cells.

On examination, there may be carti-

laginous crepitus or a crackling feel-

ing on palpation of the knee with mo -

tion. Eventually there may be coarse

bone-on-bone crepitus whereby the

opposing bone ends, denuded of carti-

lage, seem to grate against one anoth-

er. There is often a loss of range of

motion of the involved knee or hip,

particularly with progression of OA.

Loss of cartilage of the knee can

lead to malalignment of the leg with a

varus deformity or bow-legged posi-

tioning of the leg being evident. This

angulation of the knee applies to medi-

Figure 1. Radiograph of osteoarthritis ofthe hip showing predominant superolateraljoint space narrowing, subchondralsclerosis of whitening of the bone adjacentto the joint space, and some marginalosteophytes.

Figure 2. Medial compartmentosteoarthritis of the knee with medialcompartment joint space loss.This markednarrowing is between the medial tibialplateau and the medial femoral condyle.The fibula can be seen in its laterallocation.


proves the ability to diagnose mild to

moderate disease.

On plain X-ray evaluation, loss of

the radiolucent cartilage, termed joint

space narrowing, is seen in OA. In the

hip joint the joint space narrowing

tends to be more in the weight-bearing

superolateral aspect of the joint, again

highlighting the role of mechanics in

OA ( ). However, there are

different patterns of OA of the hip, and

it is possible to get more central wear,

particularly in patients with deep sock-

ets or protrusio acetabuli. In the knee,

main involvement is often in the medi-

al joint compartment ( ), but

involvement of other compartments

or of the entire joint is also common.

On plain X-ray of an osteoarthrit-

ic joint, in addition to joint space nar-

rowing, there tends to be subchondral

sclerosis or an appearance of whiten-

ing of the subchondral bone. Osteo-

phytes, which reflect a regenerative

process with formation of fibrocarti-

laginous extensions or hooks at the

joint margins, are common. Interest-

ingly, the presence of osteophytes in

one compartment, such as the lateral

compartment in a patient with medial

compartment OA, is not indicative of

disease in that compartment. It is sim-

ply indicative of the body’s reparative

response to the abnormal stresses and

presence of disease in the medial com-

partment.

The identification of OA on plain

X-rays means there is already full

thickness cartilage loss and even

bone-on-bone contact. These radi-

ographic findings occur relatively late

in the course of OA. It would be ideal

to be able to identify OA before gross

changes are apparent on radiographs.

Earlier OA detection is important in

identifying disease before the pro-

gressive bone-on-bone stage. Joint

ultrasound has been applied in studies

to identify OA earlier, but this is more

a research tool than a routine clinical

Figure 2

Figure 1

application. MRI has emerged as an

excellent modality for detection of OA

when the plain radiographs indicate

no disease or mild disease, and the

patient’s symptoms are out of keeping

with the apparent severity of disease.

MRI can detect large focal articular

cartilage lesions that cannot be detect-

ed on plain films.6-8

Classification of OATraditionally OA has been classified

as primary or secondary ( ).9

Primary OA denotes generalized or

erosive OA with no identifiable cause.

Secondary OA denotes OA caused by

an underlying condition, including

those caused by inflammatory dis-

eases, trauma, and mechanical factors.

In a large series of cases of so-

called primary osteoarthritis of the

hip, some underlying mechanical

developmental variation could be found

in most cases to account for the onset

of the disease.10 For instance, the sub-

tle presence of a shallow cup of the

hip, called acetabular dysplasia, is a

common precursor to OA of the hip.

In middle-aged men, femoroacetabu-

lar impingement (FAI) is thought to

be the most common cause of OA of

the hip. FAI of the pincer type occurs

most often in middle-aged women. On

occasion, patients may present with

symptoms of impingement prior to

the development of advanced OA. It

thus appears that the term “primary or

idiopathic OA” is probably a mis-

nomer as it applies to the hip or knee,

and that if we look hard enough an

underlying structural cause will often

be apparent.

In the 1970s Mitchell and Cruess

proposed a more pathogenetic classi-

fication of OA ( ). This classi-

fication system assumes that osteo -

arthritis can arise from an intrinsic

problem of the cartilage as encoun-

tered after years of chronic inflamma-

tory arthritis.11 Thus, OA can occur

Table 2

Table 1


Primary osteoarthritis• Idiopathic• Generalized • Erosive

Secondary osteoarthritis• Due to mechanical incongruity of joint,

congenital or acquired (e.g., acetabulardysplasia of hip or internal kneederangement)

• Due to prior inflammatory disease (e.g.,rheumatoid arthritis)

• Due to endocrine disorders (e.g.,diabetes, acromegaly)

• Due to metabolic disorders (e.g., calciumpyrrophosphate dihydrate crystals,hemochromatosis)

• Miscellaneous (e.g., avascular necrosis)

Table 1. Traditional classification of OA

Source: Adapted from Brandt KD.9

A. Abnormal concentrations of force onnormal cartilage• Cartilage surface irregularities (e.g.,

intra-articular fractures, meniscal tear)• Malalignment of the joint (e.g., leg length

disparity, acetabular dysplasia,congenital hip dislocation)

• Loss of ligamentous stability (e.g.,anterior cruciate ligament tear)

• Loss of protective sensory feedback (e.g.,diabetic neuropathy)

• Other causes (e.g., obesity, occupational)

B. Normal concentrations of force on abnormal cartilage• Pre-existing arthritis (e.g., rheumatoid

arthritis)• Metabolic abnormalities (e.g., crystal

arthropathy)• Genetic (e.g., generalized osteoarthritis

of hands)

C. Normal concentrations of force onnormal cartilage supported by stiffenedsubchondral bone• Paget disease

D. Normal concentrations of force onnormal cartilage supported by weakenedsubchondral bone• Avascular necrosis

Table 2. Classification of OA by cause

Source: Adapted from Mitchell NS, Cruess RL.11


with (A) normal force on abnormal

cartilage. Alternatively, it can occur

with (B) abnormal concentrations of

force on normal cartilage. This would

implicate mechanical aberrations such

as malalignment, the post-meniscecto-

my knee, or a cruciate deficient knee.

The abnormally formed hip mention -

ed above would fall into this category

as well.

Mitchell and Cruess’s classifica-

tion system also includes situations

where there is (C) stiffened subchon-

dral bone, as in the case of the rare

Paget disease, which does indeed pre-

dispose to OA of an involved joint.

Alternatively, they describe situations

where (D) weakened subchondreal

bone, as in avascular necrosis, predis-

poses to OA.

Risk factors for OAOA is best viewed as the end result of

an interplay between local and sys-

temic factors. Such factors are well

outlined in the classification schema

of mechanical factors proposed by

Mitchell and Cruess. Several local

systemic factors may be operative in

predisposing patients to OA of the hip

or knee.

Gender and the estrogen connectionWomen are more likely than men to

have OA, be it generalized OA of the

hands or OA of the hips and knees.12

The increase in OA in menopausal

women has led to numerous investi-

gations into the relationship between

hormonal factors and OA. The results

have been conflicting and inconclu-

sive.13,14 Clearly, other health issues

are of concern when determining

wheth er hormone replacement thera-

py is to be considered in the post-

menopausal patient.

Congenital/developmentalabnormalitiesLocal factors that affect the shape of

the joint may increase local stress on

cartilage and contribute to the devel-

opment of osteoarthritis, especially in

the hip joint. As already mentioned,

subtle and asymptomatic anatomic

variations have been associated with

hip osteoarthritis. These include ace -

tabular dysplasia or epiphysiolysis,

which are common milder variants of

congenital hip dislocation and slipped

capital femoral epiphysis, respective-

ly.10 Femoralacetabular impingement

is gaining increasing recognition as a

major structural precursor to hip OA.

These are usually asymptomatic before

possible progression to OA and can be

seen on a screening AP pelvis radi-

ograph. Such pre-symptomatic X-

rays, however, are not ordered rou-

tinely.

Genetic factorsThe strongest association between

genetic factors and OA applies to gen-

eralized osteoarthritis of the hands.

Evidence for a correlation between

genetics and knee or hip OA is less

conclusive.15,16

Physical activityAlthough the health of cartilage and

other joint tissues requires regular

joint loading, excessive loading may

contribute to OA. While some studies

suggest a strong positive relationship

between work-related knee bending

exposure and knee OA, others have

failed to find a direct relationship

between the presence of knee OA

and habitual physical activity or rec -

reational running.17 A relationship

between heavy manual work, farming

in particular, and hip OA was found in

different studies, but the association is

still considered a weak one.18

Although it makes sense that high

levels of impact and repeated torsion-

al loading could increase the risk of

articular cartilage degeneration, this

is not borne out consistently in stud-

ies. Still, it would appear prudent to

suggest that anyone with a known

underlying predisposition to OA, such

as abnormal hip or joint anatomy or

excessive body weight, avoid repeti-

tive impact-loading activities such as

jogging.

ObesityEvery step taken in a normal gait places

about three times an individual’s body

weight on lower limb joints. Thus it


Subtle and asymptomatic anatomic

variations have been associated

with hip osteoarthritis.


should not be surprising that obesity

and high body mass index have long

been recognized as potent risk factors

for OA, especially medial compart-

ment OA of the knee in females.

The Framingham Study found that

women who lost about 5 kg had a 50%

reduction in the risk of developing

new symptomatic knee OA.19 Weight-

loss interventions have been shown to

decrease pain and disability in estab-

lished knee OA. The Arthritis, Diet,

and Activity Promotion Trial showed

that weight loss combined with exer-

cise, but not either weight loss or exer-

cise alone, was effective in decreasing

pain and improving function in obese

elders who already had symptomatic

knee OA.20

When patients ask their physicians

how they can prevent OA of the knees,

weight control is paramount. Unfortu-

nately weight loss is challenging in

established OA of the knee due to the

limited physical activity possible.

The relationship between excess

weight and hip OA is less clear. The

evidence in hip OA is not as compel -

ling as with knee OA.21,22

In addition, there is evidence that

obesity predisposes to osteoarthritis

in non-weight-bearing joints such as

the joints of the hand. Clearly excess

weight in a biomechanical sense alone

does not explain this finding. Recent

studies have shown that body fat, par-

ticularly central fat deposits, are bio-

chemically active and produce sub-

stances such as leptin and adiponectin.23

It has also been shown that leptin can

induce the formation of cytokines,

such as interleukin-6, which can have

a deleterious effect on chondrocytes

of the cartilage.

TraumaIn general, there is a paucity of good

documentation to support the con-

tention that blunt trauma to a joint

increases the risk of future osteoarthri-

tis. An exception to this is the pres-

ence of intra-articular fractures, that

is, fractures that extend though the

joint line. The disruption of the carti-

lage and subchondral bone with an

intra-articular fracture does portend a

heightened risk of OA of the involved

joint in future decades. Trauma of

the knees leading to internal knee

derangement such as a mensical or

major ligamentous tear will predis-

pose to osteoarthritis. In the case of

the hip, acetabular labral tears, which

can only be seen on MRI combined

with an arthrogram, will increase the

risk of future OA of the involved hip

joint. An acetabular labral tear is often

an indication for hip arthroscopy to

trim the torn fragment. Hip arthros -

copy is not often done for diagnostic

purposes because MRI is so effective

at picking up lesions.

It is thought that blunt trauma such

as contact with a dashboard in a motor

vehicle accident can lead to patello -

femoral syndrome and chondromala-

cia patella. However, whether these

pre-OA lesions will progress in future

decades to full thickness confluent

cartilage loss signifying OA has not

been determined.

Alignment, including leg lengthStrong evidence suggests that altered

mechanics play a role in OA incidence

and progression, and recent studies

are beginning to isolate specific

mechanical factors that may be of par-

ticular importance. Such alignment

problems include a leg length discrep-

ancy of more than 1 cm, which con-

fers an increased risk of OA of the hip

on the long leg side. All patients

should be assessed for this.

Leg length measurements include

the apparent and the true leg length.

To measure leg length, you should

have the patient lie flat on his or her

back on the examining table and en -

sure that there is no hip or knee flexion

deformity that will challenge accurate

leg length measurement. It is key to

place the patient’s legs in proper align-

ment. There should be an equal dis-

tance between the medial malleoli

of the ankles, and the feet should be

centred in a neutral position under the

corresponding hips. The apparent leg

length is measured from the umbilicus

to the medial malleolus on each side.

A discrepancy usually signals a scol-

iosis. The true leg length is measured

from the anterior superior iliac spine

to the medial malleolus, and a discrep-

ancy suggests a true variation between

the two legs. For a true leg length dis-

crepancy of more than 1 cm, a shoe lift

or built-up orthotic that adjusts for half

of the leg length difference is typical-

ly recommended. For a large discrep-

ancy this may not be readily attainable.

Varus deformities, valgus deform-

i ties, and cruciate ligament tears are

other factors that can predispose to the

development and progression of knee

OA. Detailed discussion of such fac-

tors is beyond the scope of this article.

Like the medial compartment and

the lateral compartment, the patello -

femoral compartment of the knee is

often afflicted with OA. While injury

is a common factor in medial and lat-

eral compartment OA, malalignment

is a more common factor in patel-

lafemoral OA. Most cases of chon-

dromalacia patella that result from

malalignment are nonprogressive, but

some can progress to OA.24

ConclusionsOA of the hip and knee is a major

health care issue in an ever-aging pop-

ulation. OA of weight-bearing joints

confers major disability and compro-

mised quality of life. At this time,

medical treatment of OA is not as

sophisticated as the treatment of

rheumatoid arthritis. All too often we

fail with conservative treatment, and

patients with hip and knee OA progress



to total joint arthroplasty. Advances in

joint replacement seem to overshad-

ow advances in more conservative

medical treatment of OA. The better

we understand the underlying causes

and mechanisms of OA, the better we

will be equipped to develop more pro-

gressive early interventions for this

common affliction. As Ilardi and

Sokoloff, two pioneers in the study of

OA, said several decades ago, “Our

treatment of osteoarthritis can be no

more rational than our understanding

of its pathogenesis.”25

Competing interests

None declared.

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Health & Medicine

British Columbia Medical Journal, October 2010 issue: Clinical features and pathogenetic mechanisms of osteo - arthritis of the hip and knee